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Lung Non-Small Cell CarcinomaEarly Phase 1NCT05493566

Low-Dose Interleukin-2 and Pembrolizumab for the Treatment of Stage IV Non-Small Cell Lung Cancer

A Early Phase 1 study testing Aldesleukin and Pembrolizumab in people with Lung Non-Small Cell Carcinoma and Stage IV Lung Cancer AJCC v8, run by Emory University at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

This early phase 1 trial will investigate the combination of low-dose interleukin-2 (IL-2) and pembrolizumab in patients with previously untreated stage IV non-small cell lung cancer (NSCLC). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Aldesleukin and Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
1 siteUnited States
Study dates
1 Nov 2022to 7 Jan 2028
Phase
Early Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have Stage IV non-small cell lung cancer (NSCLC), based on the 8th edition of the American Joint Committee on Cancer (AJCC) NSCLC Staging System. This includes adenocarcinoma and squamous cell carcinoma.
  • Patients must have measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
  • No prior therapy for advanced NSCLC.
  • Patients with brain metastasis are eligible if they are asymptomatic or treated and stable.
  • Age greater than or equal to 18 years.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
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  • Life expectancy of greater than 12 weeks.
  • Patients must have adequate organ and marrow function, including:
  • Absolute neutrophil count (ANC) ≥ 1,500/mcL
  • Platelet count ≥ 100,000/mcL
  • Hemoglobin ≥ 9.0 g/dL (patients may be transfused to meet this)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 x institutional upper limit of normal (ULN)
  • Serum bilirubin l≤ 1.5 x ULN
  • Creatinine Clearance > 60 mL/min
  • Patients must have tumor PD-L1 expression of ≥1% (by 22c3 PD-L1 companion testing); patients whose PD-L1 status could not be determined are also eligible. Patients with known PD-L1 of 0% will be excluded.
  • For women of childbearing potential or men with sexual partners of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of < 1% per year during the treatment period and for at least 5 months after the last dose of study treatment.
  • A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (≥12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus).
  • Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
  • Ability to understand and the willingness to sign a written informed consent document.

Who cannot join

  • An individual who meets any of the following criteria will be excluded from participation in this study:
  • Any prior chemotherapy or immunotherapy for advanced lung cancer.
  • Prior treatment with anti-PD-1 or anti-PD-L1 therapies or pathway-targeting agents.
  • Any targetable driver mutation (e.g. ALK, EGFR exon 19 del, etc).
  • Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation.
  • Major surgical procedure within 28 days prior to cycle 1, day 1.
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  • Evidence of visceral crisis (severe organ dysfunction as assessed by signs, symptoms, and laboratory values, resulting from rapid progression of neoplastic disease).
  • Active concomitant malignancy that requires therapy.
  • Treatment with systemic immunosuppressive medications (e.g., prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 2 weeks prior to Cycle 1, Day 1.
  • Patients who have received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea or premedication for contrast dye allergy) are eligible.
  • The use of inhaled corticosteroids for chronic obstructive pulmonary disease (COPD) and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed.
  • History or risk of autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis
  • Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone are eligible.
  • Patients with controlled type 1 diabetes mellitus on a stable insulin regimen are eligible.
  • Patients with eczema, psoriasis, or lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible provided they meet the following conditions:
  • Rash must cover < 10% of body surface area (BSA)
  • Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%)
  • No acute exacerbations of underlying condition within the last 12 months (requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, high potency or oral steroids)
  • History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest CT scan.
  • QTc of >470 msec by EKG.
  • Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, fatty liver, and inherited liver disease.
  • Known HIV infection.
  • Active tuberculosis.
  • Administration of a live, attenuated influenza vaccine (e.g., FluMist) within 4 weeks before Cycle 1, Day 1 or at any time during the study.
  • Severe infections within 4 weeks prior to Cycle 1, Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.
  • Treatment with an investigational agent for any condition within 4 weeks prior to Cycle 1, Day 1 (or within five half-lives of the investigational product, whichever is longer).
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  • Patients who are pregnant or lactating, or who are intending to become pregnant during the study.
  • Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Suresh S. Ramalingam, MD, FACP, FASCO contact

404-778-5378

ssramal@emory.edu

Ralph Millett, MD contact

rmillet@emory.edu

United States1 site, 1 recruiting

  • Emory University/Winship Cancer Institute

    Atlanta, Georgia, 30322

    Mashunté Holmes, PhD, 404-778-1972, mashunte.holmes@emory.edu

    Suresh S. Ramalingam

    Recruiting

Other trials in United States

About this study

Official title: A Biomarker Study of Low-Dose IL-2 Plus Pembrolizumab in Patients With Stage IV Non-Small Cell Lung Cancer (NSCLC)

This early phase 1 trial will investigate the combination of low-dose interleukin-2 (IL-2) and pembrolizumab in patients with previously untreated stage IV non-small cell lung cancer (NSCLC). Preclinical data demonstrate reinvigoration of exhausted T cells into an effector-like phenotype with improved anti-tumor activity in response to this combination. This study will evaluate T cell function as well as clinical outcomes associated with this combination therapy.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To assess phenotypic, transcriptional, and epigenetic profiles of PD-1+ CD8 T cells response in patients with stage IV non-small cell lung cancer (NSCLC) treated with the combination of IL-2 and pembrolizumab.

SECONDARY OBJECTIVE:

  1. To evaluate anti-tumor activity of the combination of IL-2 and pembrolizumab by assessing the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST 1.1).

II. To evaluate the safety of the combination of IL-2 and pembrolizumab.

OUTLINE:

Patients will be treated with pembrolizumab 200 mg IV once every 3 weeks in combination with IL-2 given at 5 million IU subcutaneously twice daily for 3 weeks (5 days on, 2 days off each week, first dose in clinic and subsequent doses at home). IL-2 will be given only for the three weeks, after which pembrolizumab will be continued as monotherapy at either 200 mg every 3 weeks or 400 mg every 6 weeks.

After completion of the study treatment, patients are followed for up for 6 weeks.

Medical subject headings
Carcinoma, Non-Small-Cell Lung, Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AldesleukinBiological

    Also called 125-L-Serine-2-133-interleukin 2, Proleukin, r-serHuIL-2, Recombinant Human IL-2

    Given SC

  • PembrolizumabBiological

    Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475

    Given IV

Study groups in NCT05493566
Study groupRoleWhat they receive
Treatment (pembrolizumab, aldesleukin)ExperimentalPatients will be treated with pembrolizumab 200 mg IV once every 3 weeks in combination with IL-2 given at 5 million IU subcutaneously twice daily for 3 weeks (5 days on, 2 days off each week, first dose in clinic and subsequent doses at home). IL-2 will be given only for the three weeks, after which pembrolizumab will be continued as monotherapy at either 200 mg every 3 weeks or 400 mg every 6 weeks.
Receives: Biological: Aldesleukin; Biological: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Immune Response To Combination IL-2 and Pembrolizumab

    Percentage of patients that express a greater than 1.5-fold increase in Ki-67 + PD-L1 + CD8 T cells in peripheral blood by week 3 of combination therapy. A 95% exact confidence interval will be estimated using the Clopper-Pearson method. Descriptive statistical analysis will be utilized to determine frequencies and percentages for categorical measurements.

    Measured: Change from Baseline at weeks 1, 2, 3, 6, 12, and 18

Secondary outcomes (5)

  1. Objective Response Rate

    Will be calculated as proportion (Yes/[Yes + No]) along with 95% confidence intervals using the Clopper-Pearson method. Chi-square test or Fisher's exact test will be used to compare the response rate between the different groups stratified by dose level or other factors, respectively. Logistics regression model will be further employed to test the adjusted effect of dosage on the response rate after adjusting for other clinical factors and demographic factors.

    Measured: Up 6 weeks after study completion

  2. Progression Free Survival (PFS)

    Will be estimated alone with 95% confidence interval (CI). Cox proportional hazards models will be further used in the multivariable analyses to assess adjusted effect of dose levels on the patients' PFS after adjusting for other factors.

    Measured: 6 months, 1 year, 3 year, and 5 years

  3. Overall Survival (OS)

    Will be estimated alone with 95% CI. Cox proportional hazards models will be further used in the multivariable analyses to assess adjusted effect of dose levels on the patients' OS after adjusting for other factors.

    Measured: 6 months, 1 year, 3 year, and 5 years

  4. Dose-limiting Toxicities (DLTs)

    Will be summarized descriptively, and percentage of DLTs will be reported. Tumor response, assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, will be summarized descriptively using frequencies and percentages. Paired assessments of mean expression will be compared using paired t-tests or Wilcoxon signed rank tests, where appropriate. Statistical significance will be assessed using the 0.05 level, and analysis will be performed using SAS 9.4.

    Measured: Up 6 weeks after study completion

  5. Incidence of Adverse Events (AEs)

    The number and percentage of subjects who experience AEs will be presented in tabular and/or graphical format and summarized descriptively, where appropriate. AEs will be presented with and without regard to causality based on the investigator's judgment. The frequency of overall toxicity, categorized by toxicity grades 1 through 5, will be described. Additional summaries will be provided for AEs that are observed with higher frequency.

    Measured: Up 6 weeks after study completion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Aug 2022
  2. Study start1 Nov 2022
  3. Primary completion7 Jan 2027 (estimated)
  4. Study completion7 Jan 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
15 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05493566
Sponsor's protocol ID
STUDY00003612
Other IDs
NCI-2022-00931, STUDY00003612, WINSHIP5477-21, P30CA138292
Status last verified
Feb 2026
First submitted
2 Aug 2022
Last updated
12 Feb 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Aldesleukin and Pembrolizumab in people with Lung Non-Small Cell Carcinoma and Stage IV Lung Cancer AJCC v8, run by Emory University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 12 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Suresh S. Ramalingam, MD, FACP, FASCO (404-778-5378, ssramal@emory.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Immune Response To Combination IL-2 and Pembrolizumab (time frame: Change from Baseline at weeks 1, 2, 3, 6, 12, and 18). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05493566.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2026.

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